Container system for releasably storing a substance

ABSTRACT

The present invention provides a container system for releasably storing a substance. The container system includes a vial having a sample storage chamber and a piercing member for piercing a membrane in the lid, which membrane seals a substance within a reservoir in the lid until the membrane is pierced by the piercing member. The container system optionally includes a funnel. There is also provided a method and kit for use of such a container system.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application is a continuation of U.S. patent application Ser. No.12/096,767, which is the U.S. national stage filing under 35 U.S.C. §371of International Application No. PCT/CA2006/002009, filed Dec. 11, 2006,which claims benefit of U.S. Provisional Application No. 60/748,977,filed Dec. 9, 2005, the contents of which are hereby incorporated byreference in their entirety.

RELATED APPLICATION

This application claims priority to U.S. application Ser. No. 60/748,977filed on Dec. 9, 2005, the contents of which are hereby incorporated byreference in its entirety.

FIELD OF THE INVENTION

The field of the invention generally relates to a container system forreleasably storing a substance.

BACKGROUND

It is often desirable to store a substance, such as a liquid, solid,gas, mixtures thereof, or the like, in a container prior to mixing thecontents of the container with another material. For example, it may bedesirable to package and store a compound, or compounds, in a containerfor shipping and/or safe storage and handling, prior to combining thecompound(s) with another material. It may be desirable to package andstore a toxic compound in a container, prior to combining such a toxiccompound with a detoxifying material. As well, it is often desirable tokeep a concentrated active ingredient separate from a diluent untilimmediately prior to use.

Moreover, it may be desirable to store and/or ship diagnostic and/ornucleic acid preserving compositions prior to combining such a substancewith a biological sample.

Additionally, it may be desirable to keep a substance isolated from adonor until the donor's biological sample has been collected. This willhelp to prevent the donor from accidentally ingesting or spilling thesubstance.

It may also be desirable to inactivate pathogens/infectious particles ina biological sample, by combining it with a stored substance prior tostorage and/or shipping and/or handling of the sample.

It may also be desirable to store and/or ship diagnostic and/or nucleicacid preserving compositions after combining such a substance with abiological sample.

There are a variety of containers for holding substances separately insuch a manner that a user may open a closure to combine the substances.Typically these containers are double compartment systems in whichsubstances are stored separately and substances are combined by removalof the container closures by a user.

International PCT application WO 2003/104251 describes a container forcollecting a biological sample from a subject, and subsequently mixingthe collected sample with a composition intended to stabilize, preserve,or facilitate the recovery of components of the sample. This containerhas a first region for collecting a biological sample, a second regioncontaining a composition for preserving a nucleic acid, and a barrierbetween the first region and the second region, which when in a closedposition, maintains the sample and composition separate. The exemplifiedbarrier of WO 2003/104251 is a pivoting partition. Attachment of a lidto the container forces the barrier to pivot from its original closedposition spanning the container and thereby separating the first regionand the second region, to an open position in which both regions areexposed to each other and contact between the composition contained inone region space and the biological sample contained in the other regionis allowed. A drawback of this container is that it includes multipleparts (e.g., lid, vial, disk, rod, rod holder), which increases the costof manufacture of the container. Additionally, because the disk is heldin place by friction fit, there must be a high degree of precision forthe manufacture of the components of the container.

There remains a need for an improved container system for releasably andreliably storing a substance.

This background information is provided for the purpose of making knowninformation believed by the applicant to be of possible relevance to thepresent invention. No admission is necessarily intended, nor should beconstrued, that any of the preceding information constitutes prior artagainst the present invention.

SUMMARY OF THE INVENTION

The present invention generally relates to a container system forreleasably storing a substance.

In accordance with one aspect of the present invention, there isprovided a container system for releasably storing a substance,comprising: a) a vial comprising a first open end for receiving asample, a second end comprising a sample storage chamber and a piercingmember; and b) a lid configured to removably engage said vial, said lidcomprising a reservoir for holding the substance, and a pierceablemembrane sealing the substance within said reservoir, wherein, when saidsystem is closed by removable engagement of said vial with said lid,said vial and said lid are movable to a piercing position in which thepiercing member disrupts the pierceable membrane to allow fluidcommunication between said reservoir and said chamber, wherein thechamber is sealed against leakage to the outside of the container systemin the piercing position.

In accordance with another aspect of the present invention, there isprovided a container system for releasably storing a substance,comprising: a) a vial comprising a chamber for retaining a sample b) alid comprising a reservoir for holding the substance, and a pierceablemembrane sealing the substance within said reservoir; and c) a funnelcomprising a first open end for receiving said sample, a piercing memberand a channel extending from said first open end to a second open endand being in fluid communication with said chamber, said funnel beingremovably attachable to said lid at said first open end and releasablyor permanently attached to said vial at said second end, wherein, whensaid system is closed by removable attachment of said lid to saidfunnel, said system is movable to a piercing position in which thepiercing member disrupts the pierceable membrane to allow fluidcommunication between said reservoir and said chamber, via said channel,wherein the chamber is sealed against leakage to the outside of thecontainer system in the piercing position.

In accordance with another aspect of the present invention, there isprovided a method of combining a substance with a biological sample,comprising: (a) providing a container system as described herein; (b)providing the sample to the chamber in the vial; and (c) closing saidcontainer system by removable attachment of the lid to the vial orfunnel; and (d) piercing the membrane to release said substance intosaid chamber by moving the system to said piercing position.

In accordance with another aspect of the present invention there isprovided a kit for releasably storing a substance comprising: a) acontainer system as described herein; and b) instructions for the usethereof.

BRIEF DESCRIPTION OF THE FIGURES

FIG. 1 is a cross-sectional view of a container system in accordancewith one embodiment of the present invention, showing the lid and vialattached;

FIG. 2 is a perspective view of the interior of the lid of the containersystem depicted in FIG. 1;

FIG. 3 is a perspective view of the interior of the vial of thecontainer system depicted in FIG. 1;

FIG. 4 is a perspective view of a container system in accordance withone embodiment of the present invention;

FIG. 5 is a top view of the container system depicted in FIG. 4;

FIG. 6 is a side view of the container system depicted in FIG. 4;

FIG. 7 is a side view of the container system depicted in FIG. 4;

FIG. 8 is a bottom view of the container system depicted in FIG. 4;

FIG. 9 is a cross-sectional view of the container system of FIG. 4 takenalong line A-A in FIG. 5;

FIG. 10 is a top perspective view of the container system depicted inFIG. 4 showing the lid and vial separated;

FIG. 11 is a bottom perspective view of the container system depicted inFIG. 4 showing the lid and vial separated;

FIG. 12 is a side perspective view a container system in accordance withone embodiment of the present invention;

FIG. 13 is a top view of the container system depicted in FIG. 12;

FIG. 14 is a bottom view of the container system depicted in FIG. 12;

FIG. 15 is a side view of the container system depicted in FIG. 12;

FIG. 16 is a cross-sectional view of the container system of FIG. 12taken along line B-B in FIG. 15;

FIG. 17 is a side perspective view of the container system depicted inFIG. 12;

FIG. 18 is a top perspective view of the container system depicted inFIG. 12, showing the lid and funnel separated;

FIG. 19 is a bottom side perspective view of the container systemdepicted in FIG. 12, showing the lid and funnel separated;

FIG. 20 is a side view of the vial and cap of the container systemdepicted in FIG. 9;

FIG. 21 is a side view of the container system depicted in FIG. 12,showing the lid, funnel, and vial separated;

FIG. 22 is a side perspective view a container system in accordance withone embodiment of the present invention;

FIG. 23 is a top perspective view of the vial portion of the containersystem depicted in FIG. 22, showing the vial; and

FIG. 24 is a cross-sectional view of the lid of the container systemdepicted in FIG. 22.

The numbers in bold face type serve to identify the component parts thatare described and referred to in relation to the drawings depictingvarious embodiments of the present invention. It should be noted that indescribing various embodiments of the present invention, the samereference numerals have been used to identify the same or similarelements. Moreover, for the sake of simplicity, parts have been omittedfrom some figures of the drawings.

DETAILED DESCRIPTION OF THE INVENTION

As will be discussed in more detail below, the present inventionprovides a container system for releasably storing a substance.

The container system of the present invention has fewer parts and, thus,is less expensive and/or easier to manufacture, than previouscontainers. Additionally, the manufacturing tolerances can be lessprecise for the container system of the present invention, as comparedto previous containers having separable compartments. Again, thisreduces manufacturing cost, and makes accidental disruption of a sealedsubstance less likely. Additionally, in one example of the presentinvention, the container system includes a removable vial which issuitable for subsequent processing of samples and/or for use in roboticsystems.

The container system of the present invention comprises a vial and alid. Optionally, the container system additionally comprises a funnelthat is permanently or removably attached to the vial and that sealinglyengages the lid. The lid is configured to store a substance, andsubsequently release the substance from the lid when the lid issealingly attached to the vial, or the funnel. In use, the substancestored within the lid is released into the vial when the lid is attachedto the vial or the funnel, if present.

In accordance with a specific embodiment of the present invention, thelid is suitable to store a substance to stabilize, preserve orfacilitate the recovery of nucleic acid from a biological sample. Inaccordance with a related embodiment, the vial, or the combination ofthe funnel and vial is suitable for the collection of a biologicalsample from a subject.

Referring to the FIGS. 1-11 and 22-24, container system 300 compriseslid 100 and vial 1.

Lid

Lid 100 releasably stores a substance. Lid 100 is generallycylindrically shaped with at least one open end. Lid 100 can be avariety of shapes, as determined by the needs or preferences of the userand/or the intended application of use. The interior of lid 100 includeswall 104 that is positioned within lid 100 and defines reservoir 102 forholding a substance such as a liquid, solid, semi-solid, gas, mixturesthereof and the like. Wall 104 defines all or a portion of the perimeterof reservoir 102. Wall 104 includes sealing surface 106 which is forsealingly attaching pierceable membrane 160

Pierceable membrane 160 (depicted in FIG. 19) acts as a physical barrierto releasably store a substance within reservoir 102, when attached tosealing surface 106. Pierceable membrane 160 is made from material thatis inert to the substance to be stored within the reservoir. Pierceablemembrane 160 permits little or no diffusion of the substance throughpierceable membrane 160 over time. Pierceable membrane 160 is made froma material that is suitable for the intended processing, storage and/ortransportation conditions. In a specific embodiment, pierceable membrane160 is heat and cold resistant such that it remains intact andpierceable at temperatures ranging from about −80° C. to about +70° C.In a specific embodiment, pierceable membrane 160 can be attachedtightly enough to sealing surface 106 such that pierceable membrane 160will not be disrupted by vacuum pressures. Pierceable membrane 160 canbe made from a variety of materials including polypropylene. Desirably,pierceable membrane 160 is made from the same material as wall 104. Thethickness of pierceable membrane 160 can vary according to applicationof use, and preference of the user. Desirably, pierceable membrane 160has a thickness of about two thousandths of an inch. However, thespecific thickness of the membrane will be determined by factors suchas, nature of the substance, nature of the sample, overall dimensions ofthe container system and chemical composition of the membrane.

A variety of methods of attaching pierceable membrane 160 to sealingsurface 106 can be used, and is dependent on the material used to makelid 100, the substance stored within reservoir 102, and/or thecharacteristics of membrane 160. Such methods of attachment include useof adhesive(s), heat-sealing treatment, fasteners, or any combinationthereof, and the like. Desirably, heat-sealing is used to attachpierceable membrane 160 to sealing surface 106. As will be clear to theskilled worker, the type of pierceable membrane, the physical and/orchemical properties of the pierceable membrane will be dependent upon,in part, the composition to be stored. Desirably pierceable membrane 160is inert with respect to the intended use, stored substance and sampleof the container system.

In the specific embodiments depicted in the Figures, lid 100 comprisesinternal helical threads 108 on the inner surface of outer wall 110,which are adapted to engage external helical threads 18 on the outersurface of wall 12 on vial 1. As would be appreciated by a skilledworker, alternative means for releasable attachment of lid 100 to vial 1can be used in the container system of the present invention, providedthat lid 100 and vial 1 are movable to a piercing position, as discussedin greater detail below.

Lid 100 and reservoir 102 can be sized to accommodate a range of volumesof a substance. In the specific embodiment in which the substance is anucleic acid preservative for use with a saliva sample, reservoir 102accommodates about 1 ml to about 4 ml of a substance. The choice ofmaterial used to manufacture lid 100 is dependent upon a number offactors including manufacturing constraints, chemical suitability, andthe like. In the specific embodiment in which the substance is a nucleicacid preservative for use with a saliva sample, lid 100 is made fromplastics such us polypropylene, medium-density polyethylene (MDPE),high-density polyethylene (HDPE), polyethylene and the like. Desirably,lid 100 is polypropylene. The materials of lid 100 may be opaque,transparent or translucent, depending on the desired application. Forexample, an opaque material can be used to store a light sensitivecomposition(s). A transparent or translucent material is desirable if avisual (e.g., colour) indicator is present in the stored substance. Lid100 and reservoir 102 can be manufactured to include gradations todemarcate the quantity of the substance stored within reservoir 102. Theouter surface of lid 100 can also include a labeling area for a user toidentify the contents of the lid. The outer surface of lid 100 may alsoinclude a region to affix or emboss a logo and/or other markings.

In accordance with one embodiment of the present invention, wall 104 hasa generally cylindrical shape sized to fit within the interior of lid100. It will be clear that the shape and size of well 104 is dependentupon the intended use of the container system. Lid 100 may beconstructed from a single piece of material that includes wall 104, orwall 104 may be removably attached to lid 100. Desirably, lid 100 isformed from a single piece of material.

Vial

In accordance with one embodiment of the present invention, vial 1 isgenerally cylindrically shaped with at least one open end. Vial 1 can bea variety of shapes, as determined by the needs or preferences of theuser and/or application of use. The interior of vial 1 comprises chamber2 for receiving a sample such as a liquid, solid, semi-solid, mixturesthereof and the like. Desirably, chamber 2 is configured to receive abiological sample, for example a sputum sample, such as saliva.

Vial 1 comprises a first open end for receiving said sample, and asecond end comprising chamber 2. In one example, said second end is asecond closed end. In another example, said second end is a second openend.

In one example, the width of the first open end of vial 1 isapproximately equivalent to the width of the second end.

In another example, the first open end of vial 1 is generally wider thanthe second end vial 1. In this example, the generally wider first openend facilitates sample collection by, for example, acting similar to afunnel.

In accordance with one embodiment, and as shown in FIG. 22-24, containersystem 300 comprises a funnel fixedly attached 6, or integral with, vial1. In the case in which the funnel is fixedly attached to, or integralwith vial 1, it can also be characterised as a vial having a wide mouthopening for receiving a sample. The wide mouth or funnel characteristicscan make it easier for a subject to provide a sample.

Vial 1 and chamber 2 can be sized to accommodate a range of volumes of asample. In the specific embodiment in which the substance is a nucleicacid preservative for use with a saliva sample, chamber 2 accommodatesabout 1 ml to about 4 ml of a sample. In another specific embodiment,chamber 2 accommodates about 1 ml to about 16 ml of a sample.

Vial 1 comprises at least one piercing member 6. In the specificembodiment depicted in FIGS. 1-11 piercing member 6 extends from a basesurface of chamber 2. In one example, piercing member 6 extendsapproximately perpendicular from the base. In another example, piercingmember 6 is angled inwardly or outwardly toward the open end of vial 1.Alternatively, piercing member 6 extends from an interior surface ofsaid vial. In one example, piercing member 6 extends from an interiorsurface of said vial and is angled inwardly or outwardly toward the openend of vial 1.

In one example, there is one piercing member 6 within chamber 2. In analternative example, there is a plurality of piercing members 6, forexample, two piercing members, three piercing members or more than threepiercing members. In one example the piercing members are arranged in agenerally semicircular fashion. In a specific example, in the case ofthree piercing members, the piercing members are arranged in a generallysemicircular fashion, as depicted in FIGS. 9, 10 and 23.

Piercing member 6 can be approximately trapezoidal in shape and includesfirst cutting edge 33 having pointed end 30 at one corner of thetrapezoid and a second end at a second corner of the trapezoid wherecutting edge 32 intersects side wall 34. Optionally, side wall 34 alsoincludes cutting edge 33, which extends from cutting edge 32.

Container system 300 further includes a means for sealing attachment oflid 1 to vial 100. Such sealing means act to ensure that the contents ofvial 1 remain sealed with chamber 2 when lid 100 is attached to vial 1.

In one example, lid 100 and vial 1 are movable between an open positionand a piercing position. In a specific example, lid 100 is initiallyattached to vial 1 by threadingly engaging internal and external threads108 and 18 with a twisting motion. Initially, lid 100 and vial 1 arethreadingly connected, but piercing member 6 does not disrupt pierceablemembrane 160 and end portion 30 of wall 12 engages sealing wall 120. Forexample, as depicted in FIG. 9, sealing wall 120 extends downwardly andoutwardly from the interior of lid 100. This type of sealing mechanismis similar to a wipe seal that would be well known to the skilledworker. Thus, initially, chamber 2 is maintained out of fluidcommunication with reservoir 102 by pierceable membrane 160.

In an alternate example, lid 100 and vial 1 are movable between a firstposition and a piercing position. In a specific example, lid 100 isinitially attached to vial 1 by threadingly engaging internal andexternal threads 108 and 18 with a twisting motion and thereby moved tothe first position. In moving lid 100 and vial 1 to the first position,lid 100 and vial 1 are threadingly connected, but piercing member 6 doesnot disrupt pierceable membrane 160. In the first position, end portion30 of wall 12 sealingly engages sealing wall 120. For example, asdepicted in FIG. 9, sealing wall 120 extends downwardly and outwardlyfrom the interior of lid 100. This type of sealing mechanism is similarto a wipe seal that would be well known to the skilled worker. Thus, inthe first position, chamber 2 is sealed against leakage to the outsideof the container system by sealing engagement of wall 12 with sealingwall 120 and maintained out of fluid communication with reservoir 102 bypierceable membrane 160.

A worker skilled in the art will recognize that there are knownalternative sealing structures that can be incorporated into the presentsystem for ensuring that chamber 2 is sealed against leakage to theoutside of the container system. Such alternatives are considered to bewithin the scope of the present invention.

Continued twisting moves lid 100 and vial 1 from the open position, orthe first position, to the piercing position, in which movement of lid100 and vial 1 together results in disruption of pierceable membrane 160by piercing member 6, and the release of the substance within reservoir102 into chamber 2.

In operation, in moving to the piercing position, pointed end 31 ofpiercing member 6 is brought into contact with pierceable membrane 160and pierces pierceable membrane 160. Continued twisting moves cuttingedge 32 through pierceable membrane 160, disrupting pierceable membrane160, and thereby producing an opening in the sealing membrane to enablethe substance to enter chamber 2. It will be clear that if more than onepiercing member is present, less twisting of lid 100 and vial 1 isrequired to generate an opening. When three piercing members arepresent, a suitable opening is obtainable in about one quarter of aturn. Desirably, pierceable membrane 160 is not completely removed fromsealing surface 106. Thus, in the piercing position, piercing member 6disrupts pierceable membrane 160 to allow fluid communication betweenreservoir 102 and chamber 2.

The distance between piercing member 6 and wall 104 will vary accordingto the needs and preferences of the user. The distance between piercingmember 6 and wall 104 can vary from being generally flush with oneanother, to being generally separated from one another.

It will be clear to the skilled worker that length, rigidity and thelike, of piercing member 6 is selected such that it is sufficient todisrupt pierceable membrane 160 when lid 100 and vial 1 are in thepiercing position, and not disrupt the pierceable membrane 160 when lid100 and vial 1 are in the open or first position.

The choice of the material of vial 1 will be dependent upon a number offactors including manufacturing constraints, chemical suitability, andthe like. Additionally, the construction material of lid 1 may be sameor different as that used to make reservoir 6. In the specificembodiment in which the substance is a nucleic acid preservative for usewith a saliva sample, vial 1 is made from plastics such uspolypropylene, medium-density polyethylene (MDPE), high-densitypolyethylene (HDPE), polyethylene and the like. Desirably, vial 1 isHDPE.

In accordance with another aspect of the present invention, thecontainer system comprises a lid, a funnel and a vial.

Referring to the FIGS. 12-21, container system 600 comprises lid 100 andfunnel 400 and vial 500.

Lid

Lid 100 releasably stores a substance, as described above.

Funnel

Funnel 400 includes a first open end for receiving a sample, a secondopen end for removable or fixed attachment to vial 500. In oneembodiment, funnel 400 is integral with vial 500. The interior of funnel400 comprises interior channel 422 extending therethrough formaintaining the first open end and the second open end in fluidcommunication and for receiving a sample such as a liquid, solid,semi-solid, mixtures thereof and the like. Funnel 400 can be a varietyof shapes, as determined by the needs or preferences of the user and/orapplication of use. Desirably, interior channel 422 is configured toreceive a biological sample. For example, the biological sample is asputum sample, such as saliva. Interior channel 422 can be sizedaccommodate a range of volumes of sample.

In the specific embodiments depicted in the Figures, lid 100 comprisesinternal helical threads 108 on the inner surface of outer wall 110,which are adapted to engage external helical threads 418 on the outersurface of wall 412 on funnel 400. As would be appreciated by a skilledworker, alternative means for releasable attachment of lid 100 to funnel400 can be used in the container system of the present invention,provided that lid 100 and funnel 400 are movable to the piercingposition, as discussed in greater detail above.

Funnel 400 comprises at least one piercing member 6. In accordance withthe embodiment depicted in FIGS. 12-21, piercing member 6 extends froman interior surface (interior side wall 420) of funnel 400. In oneexample, piercing member 6 is angled inwardly or outwardly towardpierceable membrane 160. Other arrangements of piercing member 6 can beused, as would be readily appreciated by the skilled worker.

In one example, there is one piercing member 6 within interior channel422. In an alternative example there is a plurality of piercing members,for example, two piercing members, three piercing members or more thanthree piercing members. In the case of three piercing members, desirablythe piercing members are arranged in a generally semicircular fashion,as shown in FIG. 18.

As above, piercing member 6 can be approximately trapezoidal in shapeand includes first cutting edge 33 having pointed end 30 at one cornerof the trapezoid and a second end at a second corner of the trapezoidwhere cutting edge 32 intersects side wall 34. Optionally, side wall 34also includes cutting edge 33, which extends from cutting edge 32.

Container system 600 further includes a means for sealing attachment oflid 1 to funnel 400. Such sealing means act to ensure that the contentsof vial 1 remain sealed with chamber 2 when funnel 400 and vial 500 areattached to vial 1.

Optionally, funnel 400 includes outwardly extending ribs 402 that canused by a user to twist funnel 400 and lid 100, and/or funnel 400 andvial 500.

The choice of the material of funnel 400 will be dependent upon a numberof factors including manufacturing constraints, chemical suitability,and the like. Additionally, the construction material of funnel 400 maybe same or different as that used to make lid 100 and collection vial500. In the specific embodiment in which the substance is a nucleic acidpreservative for use with a saliva sample, funnel 400 is made fromplastics such us polypropylene, high-density polyethylene (HDPE),polyethylene, medium-density polyethylene (MDPE), or any combinationthereof, and the like. Desirably, vial 1 is HDPE.

In a specific example, lid 100 is polypropylene, vial 500 ispolypropylene and funnel 400 is HDPE.

Vial

Vial 500 (or collection vial 500) is generally cylindrically shaped withan open end for removable or fixed attachment to the second end offunnel 400, and chamber 530 for receiving a sample. Vial 500 can be avariety of shapes, as determined by the needs or preferences of the userand/or application of use, and can be specifically manufactured for usein the container system of the present invention or can be acommercially available vial. As noted above, and in one embodiment,funnel 400 is integral with vial 500. When the container system is usedfor laboratory purposes, desirably, vial 500 is sized to fit within astandard test tube rack such as that typically used in biological sampleprocessing. In one example, vial 500 conforms with industry-standarddimensions for blood collection tubes (e.g., 13 mm×75 mm). Desirablyvial 500 is suitable for use with robotic DNA purification systems(e.g., the Beckman BioMek™ FX). Desirably, vial 500 is commerciallyavailably from Simport Plastics Limited (e.g., the T501 tubes).

The open end of vial 500 is also configured for securing attachment witha standard cap 520, as shown in FIG. 21. Cap 520 can be secured by athreaded screw, snap-fit, and the like.

Vial 500 optionally includes surface 502 that is suitable for labelingand/or for providing friction for gripping by a user.

Vial 500 may be removably attached to funnel 400 using a variety oflocking mechanisms. In accordance with one embodiment of the presentinvention, the locking mechanism is a helical threaded screw.Alternatively, the locking mechanism is a snap-fit. Alternatively, vial500 is fixedly attached to, or integral with, funnel 400.

In one example, lid 100 and funnel 400 are movable between an openposition and a piercing position, as discussed supra with lid 100 andvial 1. In a specific example, lid 100 is initially attached to funnel400 by threadingly engaging internal and external threads 108 and 18with a twisting motion. Initially, lid 100 and funnel 400 arethreadingly connected, but piercing member 6 does not disrupt pierceablemembrane 160, and end portion 30 of wall 12 engages sealing wall 120. Asdepicted in FIGS. 9 and 16, sealing wall 120 extends downwardly andoutwardly from the inner surface of lid 100. This type of sealingmechanism is similar to a wipe seal, that would be well known to theskilled worker. Thus, initially, interior channel 422 is maintained outof fluid communication with said reservoir 102 by pierceable membrane 6.

In an alternate example, lid 100 and funnel 400 are movable between afirst position and a piercing position, as discussed supra with lid 100and vial 1. Lid 100 is initially attached to funnel 400 by threadinglyengaging internal and external threads 108 and 18 with a twistingmotion. In moving lid 100 and funnel 400 to the first position, lid 100and funnel 400 are threadingly connected, but piercing member 6 does notdisrupt pierceable membrane 160. In the first position, end portion 30of wall 12 sealingly engages sealing wall 120. As depicted in FIGS. 9and 16, sealing wall 120 extends downwardly and outwardly from the innersurface of lid 100. This type of sealing mechanism is similar to a wipeseal, that would be well know to the skilled worker. Thus, in the firstposition, interior channel 422 is sealed against leakage to the outsideof the container system and maintained out of fluid communication withsaid reservoir 102 by pierceable membrane 6.

Continued twisting moves lid 100 and funnel 400 from either the openposition or the first position, to the piercing position, in whichmoving lid 100 and vial 1 together results in disruption of pierceablemembrane 160 by piercing member 6, and the release of the substancewithin reservoir 102 into chamber 2 and vial 500.

In operation, in moving to the piercing position, pointed end 30 isbrought into contact with pierceable membrane 160 and subsequentlypierces pierceable membrane 160. Continued twisting moves cutting edge32 through pierceable membrane 160, thereby disrupting pierceablemembrane 160 and producing an opening in pierceable membrane 160 topermit the substance to enter interior channel 422. If more than onepiercing member is present, less twisting of lid 100 and vial 1 isrequired to generate an opening. When three piercing members arepresent, a suitable opening is obtainable in about one quarter of aturn. Thus, in the piercing position, piercing member 6 disruptspierceable membrane 160 to allow fluid communication between reservoir102 and interior channel 422.

The distance between piercing member 6 and wall 104 will vary accordingto the needs and preferences of the user. The distance between piercingmember 6 and wall 104 can vary from being generally flush with oneanother, to being generally separated from one another.

It will be clear to the skilled worker that length, rigidity and thelike, of piercing member 6 is selected such that it sufficient todisrupt pierceable membrane 160 when lid 100 and vial 1 are in thepiercing position, and not disrupt the pierceable membrane 160 when lid100 and vial 1 are in the open or first position.

Methods

According to one embodiment of the present invention, the containersystem of the present application is suitable for releasably storing acomposition intended to stabilize, preserve, or facilitate the recoveryof nucleic acid from a biological sample. A biological sample caninclude bodily fluids and/or tissues.

Desirably, vial 1 and/or funnel 400 are sized for collecting abiological sample from a subject. Non-limiting examples of biologicalsamples include skin, hair, fecal matter, bodily fluids, tissue, cellsand the like.

The term “bodily fluid”, as used herein, refers to a naturally occurringfluid from a human or an animal, such as saliva, sputum, serum, plasma,blood, pharyngeal, nasal/nasal pharyngeal and sinus secretions, urine,mucus, gastric juices, pancreatic juices, feces, semen, products oflactation or menstruation, tears, or lymph.

The term “bodily tissue” or “tissue”, as used herein, refers to anaggregate of cells usually of a particular kind together with theirintercellular substance that form one of the structural materials of aplant or an animal and that in animals include connective tissue,epithelium, muscle tissue, and nerve tissue, and the like.

The term “nucleic acid”, as used herein, refers to a chain ofnucleotides, including deoxyribonucleic acid (DNA) or ribonucleic acid(RNA), typically found in chromosomes, chromatin, mitochondria,ribosomes, cytoplasm, nucleus, microorganisms or viruses.

The term “ribonucleic acid” or “RNA”, as used herein, refers to a widerange of RNA species, including, but not limited to high molecular RNA,large and small ribosomal RNAs, messenger RNA, pre-messenger RNA, smallregulatory RNAs, RNA viruses (single and double-stranded, positivestranded or negative stranded) and the like. The RNA may be from avariety of sources, including, but not limited to human, non-human,viral, bacterial, fungal, protozoan, parasitic, single-celled,multi-cellular, in vitro, in vivo, natural, and/or synthetic sources.

Optionally the bodily fluid is saliva. The term “saliva”, as usedherein, refers to the secretion, or combination of secretions, from anyof the salivary glands, including the parotid, submaxillary, andsublingual glands, optionally mixed with the secretions from thenumerous small labial, buccal, and palatal glands that line the mouth.

The term “subject”, as used herein, refers to an animal or human.Desirably, the subject is a mammal that can produce saliva for thepurposes of nucleic acid stabilization and/or detection. Most desirably,the subject is human.

In use, a substance, such as a composition intended to stabilize,preserve, or facilitate the recovery of nucleic acid from a biologicalsample is sealed within reservoir 102 with a pierceable membrane.Suitable compositions include those described in International PCTapplication WO 2003/104251; International PCT applicationPCT/CA2006/000380; U.S. application Ser. Nos. 60/828,563; or 60/866,985,all of the contents of which are hereby incorporated by reference intheir entirety. Desirably the composition is Oragene™ DNA-preservingsolution. Other suitable compositions would be well known to the skilledworker.

In use, in one example, a sample of saliva from a subject is placedwithin chamber 2 of vial 1. Alternatively, vial 500 is attached tofunnel 400, and a sample of saliva is placed within chamber 2 of funnel400.

To collect saliva from a subject, in one example, the subject isinstructed to wait for a period of 30-60 minutes before last eating. Ifpossible, the subject will brush his teeth (without using toothpaste).If possible, the subject will rinse his/her mouth with 50 ml of water.The subject will be requested to wait for 5-10 minutes to allow themouth to clear of water. For subjects able to spit, they will beinstructed to spit saliva into the special collection vial until thelevel of saliva reaches the 1 or 2 ml mark. Waiting after last eatingand rinsing the mouth is desirable but not essential. Collection ofsaliva may take several minutes. If the subject finds that he/she isunable to deliver sufficient saliva, he/she will be given a few grainsof table sugar to chew, and told not to be concerned if some of thesugar is spit into the vial. For subjects unable to spit (e.g., infants,young children, individuals with limitations/disabilities), an implement(e.g., swab, transfer pipette) may be used for sample collection.Similarly, a subject may be provided a liquid (e.g., mouthwash, water,saline) to gargle his/her mouth and throat or saline to flush his/hernasal cavity. Samples collected with said liquid would be delivered intothe collection vial.

A substance, such as a composition to stabilize, preserve, and/orfacilitate the recovery of nucleic acid and saliva is stored withinreservoir 102 of lid 100.

Lid 100 is then attached to vial 1, moved to the piercing position, andthe substance combines with the saliva in chamber 2.

Alternatively, lid 100 is attached to funnel 400, moved to the piercingposition, and the substance combines with the saliva in interior 530.

The combination of the composition to stabilize, preserve, or facilitatethe recovery of nucleic acid and saliva may then be used in standardnucleic acid testing reactions, for example for detection orquantitation. Alternatively, the combination may be stored withincontainer system 300 or 600 and subsequently used, for example, fordetection of nucleic acid contained within the saliva. Alternatively,funnel 400 is removed from vial 500, and cap 520 is attached to the openend of vial 500. In this example, the combination may be stored withinvial 500 and subsequently used, for example, for detection of nucleicacid contained within the saliva.

In one aspect of the present invention container system 300 andcontainer system 600 are sized for shipping. In one example, vial 1 andlid 100 of container system 300 are sized for shipping when securelyattached. In one example lid 1, funnel 400 and collection vial 500 ofcontainer system 600, are sized for shipping when lid 1, funnel 400 andcollection vial 500 are securely attached. In another example, vial 1and lid 100 of container system 300 are sized for shipping when vial 1and lid 100 are separate. In another example, lid 1, funnel 400 andcollection vial 500 of container system 600, are sized for shipping whenlid 1, funnel 400 and collection vial 500 are separate. It will beappreciated that a variety methods of shipping are contemplated.Non-limiting examples of shipping include shipping by hand, land, air,boat, animal, and the like, or combinations thereof. Desirably,container system 300 or container system 600 fit within a standard mailenvelope. In one example, container system 300 or container system 600fit within an envelope sized to fit within a standard European mailslot. In a specific example, the standard European mail slot has a widthof about 3 cm. Alternatively, container system 300 or container system600 fit within an envelope sized to fit within a standard Canadianand/or United States of America mail slot.

Another aspect of the present invention provides a method of manufactureof a device for releasably storing a substance. The method ofmanufacture comprises providing container system in accordance with thepresent invention.

Another aspect of the present invention provides a method of combining asubstance with a biological sample. This method comprises providing acontainer system in accordance with the present invention, wherein thecontainer system includes the substance, and providing the biologicalsample.

Another aspect of the present invention provides a method of preservingnucleic acid in a biological sample. This method comprises providing acontainer system in accordance with the present invention, wherein thecontainer system includes a substance for preserving nucleic acid in abiological sample.

Another aspect of the present invention provides a method of archiving abiological sample for prolonged periods of time. Desirably archiving isat room temperature. This method comprises providing a container systemin accordance with the present invention and providing a substance forarchiving the biological sample. In one example, prolonged storage is atroom temperature for more than about one week, about two weeks, aboutthree weeks, about one month, more than about one month, about one year.

Kit

Another aspect of the present invention provides a kit for collection ofa sample and mixing the sample with a substance. The kit includes acontainer system in accordance with the present invention andinstructions for the use thereof, optionally with a substance storedwithin the lid of the container system.

All publications, patents and patent applications mentioned in thisSpecification are indicative of the level of skill of those skilled inthe art to which this invention pertains and are herein incorporated byreference to the same extent as if each individual publication, patent,or patent applications was specifically and individually indicated to beincorporated by reference.

The invention being thus described, it will be obvious that the same maybe varied in many ways. Such variations are not to be regarded as adeparture from the spirit and scope of the invention, and all suchmodifications as would be obvious to one skilled in the art are intendedto be included within the scope of the following claims.

The embodiments of the invention in which an exclusive property orprivilege is claimed are defined as follows:
 1. A container system forreleasably storing a substance, comprising: a) a vial comprising a firstopen end for receiving a sample, a second end comprising a samplestorage chamber and at least two piercing members, wherein: i) each ofsaid at least two piercing members comprises a side wall, a firstcutting edge extending from a first pointed end to a second end thatdefines the intersection between said cutting edge and said side wall,and/or ii) said at least two piercing members are arranged in asemi-circular fashion; and b) a lid configured to removably engage saidvial, said lid comprising a reservoir for holding the substance, and apierceable membrane sealing the substance within said reservoir,wherein, when said system is closed by removable engagement of said vialwith said lid, said vial and said lid are movable to a piercing positionin which the piercing members disrupt the pierceable membrane to allowfluid communication between said reservoir and said chamber, wherein thechamber is sealed against leakage to the outside of the container systemin the piercing position.
 2. The container system of claim 1, whereinsaid lid comprises a wall defining all or a portion of the perimeter ofsaid reservoir, said wall having a sealing surface for sealinglyattaching said pierceable membrane.
 3. The container system of claim 1,wherein said reservoir is configured to retain about 1 ml to about 4 mlof said substance.
 4. The container system of claim 1, wherein saidpierceable membrane is inert.
 5. The container system of claim 1,wherein said pierceable membrane remains intact and pierceable attemperatures of from about −80° C. to about 70° C.
 6. The containersystem of claim 1, wherein said pierceable membrane is sealinglyattached to said sealing surface by an adhesive, a heat-sealingtreatment, a fastener, or any combinations thereof.
 7. The containersystem of claim 1, wherein the width of said first end is equivalent tothe width of said second end.
 8. The container system of claim 1,wherein said first end is generally wider than said second end.
 9. Thecontainer system of claim 1, wherein said chamber is configured toreceive about 1 ml to about 16 ml of said sample.
 10. The containersystem of claim 9, wherein said chamber is configured to receive about 1ml to about 4 ml of said sample.
 11. The container system of claim 1,wherein the said at least two piercing members extend from a basesurface or an interior side surface of said chamber.
 12. The containersystem of claim 11, wherein said at least two piercing members extendapproximately perpendicularly from said base.
 13. The container systemof claim 11, wherein said at least two piercing members are angledinwardly or outwardly toward said first open end of said vial.
 14. Thecontainer system of claim 1, wherein said side wall further includes asecond cutting edge.
 15. The container system of claim 1, wherein saidat least two piercing members are arranged in a semi-circular fashion.16. The container system of claim 1, wherein said vial comprises threepiercing members.
 17. The container system of claim 1, wherein each ofsaid at least two piercing members additionally comprises a secondpointed end corner.
 18. The container system of claim 1, wherein saidsystem comprises a seal for sealing said chamber against leakage to theoutside of said container system following movement of said containersystem to said piercing position.
 19. The container system of claim 18,wherein said seal comprises a sealing wall about the interiorcircumference of said lid that sealingly engages a surface of said vialwhen the system is in said piercing position.
 20. The container systemof claim 1, wherein said vial and said lid are sized for shipping inboth an unattached state and an attached state.
 21. A container systemfor releasably storing a substance, comprising: a) a vial comprising achamber for retaining a sample; b) a lid comprising a reservoir forholding the substance, and a pierceable membrane sealing the substancewithin said reservoir; and c) a funnel comprising: (i) a first open endfor receiving said sample; (ii) an interior conical wall defining achannel connecting said first open end to a second open end that is influid communication with said chamber and that has a smaller diameterthan the diameter of said first open end; and (iii) at least twopiercing members extending from said interior conical wall, said funnelbeing removably attachable to said lid at said first open end andreleasably or permanently attached to said vial at said second end;wherein, when said system is closed by removable attachment of said lidto said funnel, said system is movable to a piercing position in whichthe at least two piercing members disrupt the pierceable membrane toallow fluid communication between said reservoir and said chamber, viasaid channel, wherein the chamber is sealed against leakage to theoutside of the container system in the piercing position and wherein: 1)each of said at least two piercing members comprises a side wall, and afirst cutting edge extending from a first pointed end to a second endthat defines the intersection between said cutting edge and said sidewall, and/or 2) said at least two piercing members are arranged in asemi-circular fashion.
 22. The container system of claim 21 wherein saidlid comprises a wall defining all or a portion of the perimeter of saidreservoir and including a sealing surface for sealingly attaching saidpierceable membrane.
 23. The container system of claim 21, wherein saidreservoir is configured to retain about 1 ml to about 4 ml of saidsubstance.
 24. The container system of claim 21, wherein said pierceablemembrane is inert.
 25. The container system of claim 21, wherein saidpierceable membrane maintains intact and pierceable at temperatures offrom about −80° C. to about 70° C.
 26. The container system of claim 21,wherein said pierceable membrane is sealingly attached to said sealingsurface by an adhesive, a heat-sealing treatment, a fastener, or anycombinations thereof.
 27. The container system of claim 21, wherein saidat least two piercing members extend from an interior surface of saidfunnel.
 28. The container system of claim 27, wherein said at least twopiercing members are angled inwardly or outwardly toward said first openend of said funnel.
 29. The container system of claim 21, wherein saidside wall includes a second cutting edge.
 30. The container system ofclaim 21, wherein said at least two piercing members are arranged in asemi-circular fashion.
 31. The container system of claim 21, whereinsaid funnel comprises three piercing members.
 32. The container systemof claim 21, wherein said funnel comprises two piercing members.
 33. Thecontainer system of claim 21, wherein said system comprises a seal forsealing said chamber against leakage to the outside of said containersystem.
 34. The container system of claim 33, wherein said sealcomprises a sealing wall about the interior circumference of said lidthat sealingly engages a surface of said funnel when the system is inthe piercing position.
 35. The container system of claim 21, whereinsaid vial is releasably attached to said funnel and sized for attachmentto a cap when released from said funnel.
 36. The container system ofclaim 21, wherein said each of said at least two piercing membersadditionally comprises a second pointed end.
 37. The container system ofclaim 21, wherein said at least two piercing members extend from saidinterior conical wall at a position adjacent to said second open end.38. The container system of claim 37, wherein said vial is a T501 tube.39. The container system of claim 21, wherein said chamber is sized tohold about 1 ml to about 16 ml.
 40. The container system of claim 21,wherein said substance is a composition for the stabilization andrecovery of a nucleic acid from a biological sample.
 41. The containersystem of claim 40, wherein said nucleic acid is DNA or RNA.
 42. Amethod of combining a substance with a biological sample, comprising:(a) providing a container system of claim 1; (b) providing the sample tothe chamber in the vial; and (c) closing said container system byremovably attaching said lid to said vial; and (d) piercing saidmembrane to release said substance into said chamber by moving said lidand said vial to said piercing position.
 43. A method of combining asubstance with a biological sample, comprising: (a) providing acontainer system of claim 21; (b) providing the sample to the chamber inthe vial through said funnel; and (c) closing said container system byremovably attaching said lid to said first open end of said funnel; and(d) piercing said membrane to release said substance into said chamberby moving said system to said piercing position.
 44. The method of claim43, wherein the substance is a preservative.
 45. The method of claim 43,wherein the sample is a biological sample.
 46. The method of claim 43,for archiving the sample.
 47. A kit for sample collection and storage,comprising: a) a container system of claim 21; and b) instructions forthe use thereof.
 48. The method of claim 44, wherein the preservative isa nucleic acid preserving substance.
 49. The method of claim 43,additionally comprising: (e) removing said lid and funnel from saidvial; and (f) attaching a cap to the open end of said vial.
 50. Thecontainer system of claim 1, wherein the substance is a liquid.
 51. Thecontainer system of claim 21, wherein the substance is a liquid.
 52. Thecontainer system of claim 1, additionally comprising a solid orsemi-solid material within said vial and maintained separate from thesubstance in the reservoir of said lid until said pierceable membrane isdisrupted.
 53. The container system of claim 21, additionally comprisinga solid or semi-solid material within said vial and maintained separatefrom the substance in the reservoir of said lid until said pierceablemembrane is disrupted.
 54. The container system of claim 1, wherein saidsubstance is a composition for the stabilization and recovery of anucleic acid from a biological sample.
 55. The container system of claim54, wherein said nucleic acid is DNA or RNA.
 56. The method of claim 42,wherein the substance is a preservative.
 57. The method of claim 56,wherein the preservative is a nucleic acid preserving substance.
 58. Themethod of claim 42, wherein the sample is a biological sample.
 59. Themethod of claim 42, for archiving the sample.
 60. A kit for samplecollection and storage, comprising: a) a container system of claim 1;and b) instructions for the use thereof.
 61. The container system ofclaim 15, wherein said vial comprises three piercing members that arearranged in a semi-circular fashion.
 62. The container system of claim30, wherein said vial comprises three piercing members that are arrangedin a semi-circular fashion.
 63. A method of combining a substance with abiological sample, comprising: (a) providing a container system of claim15; (b) providing the sample to the chamber in the vial; and (c) closingsaid container system by removably attaching said lid to said vial; and(d) piercing said membrane to release said substance into said chamberby moving said lid and said vial to said piercing position.
 64. A methodof combining a substance with a biological sample, comprising: (a)providing a container system of claim 30; (b) providing the sample tothe chamber in the vial through said funnel; and (c) closing saidcontainer system by removably attaching said lid to said first open endof said funnel; and (d) piercing said membrane to release said substanceinto said chamber by moving said system to said piercing position.
 65. Akit for sample collection and storage, comprising: a) a container systemof claim 15; and b) instructions for the use thereof.
 66. A kit forsample collection and storage, comprising: a) a container system ofclaim 21; and b) instructions for the use thereof.
 67. The containersystem of claim 1, wherein each of said at least two piercing memberscomprises a side wall, a first cutting edge extending from a firstpointed end to a second end that defines the intersection between saidcutting edge and said side wall.
 68. The container system of claim 30,wherein each of said at least two piercing members comprises a sidewall, a first cutting edge extending from a first pointed end to asecond end that defines the intersection between said cutting edge andsaid side wall.
 69. A method of combining a substance with a biologicalsample, comprising: (a) providing a container system of claim 67; (b)providing the sample to the chamber in the vial; and (c) closing saidcontainer system by removably attaching said lid to said vial; and (d)piercing said membrane to release said substance into said chamber bymoving said lid and said vial to said piercing position.
 70. A method ofcombining a substance with a biological sample, comprising: (a)providing a container system of claim 68; (b) providing the sample tothe chamber in the vial through said funnel; and (c) closing saidcontainer system by removably attaching said lid to said first open endof said funnel; and (d) piercing said membrane to release said substanceinto said chamber by moving said system to said piercing position.
 71. Akit for sample collection and storage, comprising: a) a container systemof claim 67; and b) instructions for the use thereof.
 72. A kit forsample collection and storage, comprising: a) a container system ofclaim 68; and b) instructions for the use thereof.
 73. The containersystem of claim 1, wherein each of said at least two piercing memberscomprises a side wall, a first cutting edge extending from a firstpointed end to a second end that defines the intersection between saidcutting edge and said side wall, and said at least two piercing membersare arranged in a semi-circular fashion.
 74. The container system ofclaim 21, wherein each of said at least two piercing members comprises aside wall, a first cutting edge extending from a first pointed end to asecond end that defines the intersection between said cutting edge andsaid side wall, and said at least two piercing members are arranged in asemi-circular fashion.
 75. A method of combining a substance with abiological sample, comprising: (a) providing a container system of claim73; (b) providing the sample to the chamber in the vial; and (c) closingsaid container system by removably attaching said lid to said vial; and(d) piercing said membrane to release said substance into said chamberby moving said lid and said vial to said piercing position.
 76. A methodof combining a substance with a biological sample, comprising: (a)providing a container system of claim 74; (b) providing the sample tothe chamber in the vial through said funnel; and (c) closing saidcontainer system by removably attaching said lid to said first open endof said funnel; and (d) piercing said membrane to release said substanceinto said chamber by moving said system to said piercing position.
 77. Akit for sample collection and storage, comprising: a) a container systemof claim 73; and b) instructions for the use thereof.
 78. A kit forsample collection and storage, comprising: a) a container system ofclaim 74; and b) instructions for the use thereof.